One of the most essential functions of blood is to transport a sufficient and continuous supply of oxygen from the lungs to the tissues. The efficiency of blood oxygen transport depends highly on the oxygen binding properties of red cell hemoglobin. We have been studying the oxygen binding properties of normal, abnormal, and chemically modified hemoglobin under various physiological and drug conditions. By preparing a number of artificial hemoglobins that contain chemically modified hemes, we found that certain modifications not only increase the oxygen unloading capacity of hemoglobin but decrease the rate of oxidation of heme into methemoglobin. Since these hemoglobins can be prepared on a large scale, these basic studies will be the foundation for preparing artificial blood in the future. Some of the synthetic proteins, including green myoglobin and heme-spin-labeled hemoglobin, that have the same oxygen binding properties as those of native proteins can be used as markers for determining properties of native hemoglobins. Other synthetic hemo-proteins can be used as reporter molecules for abnormal hemoglobins. These synthetic hemoglobins will also be incorporated into the red cell membrane in order to study the oxygen transport through the red cell membrane. In addition, the mechanism of oxygen supply to tissue will be studied by using organ perfusion and surface fluorometric techniques. These fundamental studies of hemoglobin will provide a basis for further understanding and treatment of hemoglobinopathies and disorders of oxygen transport.